title: Interferon regulatory factor 1 polymorphisms previously associated with reduced HIV susceptibility have no effect on HIV disease progression.
abstract: BACKGROUND
  Interferon regulatory factor 1 (IRF1) is induced by HIV early in the infection process and serves two functions: transactivation of the HIV-1 genome and thus replication, and eliciting antiviral innate immune responses. We previously described three IRF1 polymorphisms that correlate with reduced IRF1 expression and reduced HIV susceptibility.
  
  
  OBJECTIVE
  To determine whether IRF1 polymorphisms previously associated with reduced HIV susceptibility play a role in HIV pathogenesis and disease progression in HIV-infected ART-naïve individuals.
  
  
  METHODS
  IRF1 genotyping for polymorphisms (619, MS and 6516) was performed by PCR in 847 HIV positive participants from a sex worker cohort in Nairobi, Kenya. Rates of CD4+ T cell decline and viral loads (VL) were analyzed using linear mixed models.
  
  
  RESULTS
  Three polymorphisms in the IRF1, located at 619, microsatellite region and 6516 of the gene, previously associated with decreased susceptibility to HIV infection show no effect on disease progression, either measured by HIV-1 RNA levels or the slopes of CD4 decline before treatment initiation.
  
  
  CONCLUSIONS
  Whereas these three polymorphisms in the IRF1 gene protect against HIV-1 acquisition, they appear to exert no discernable effects once infection is established.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Aida
authors.initials: A
authors.lastname: Sivro
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: Hezhao
authors.initials: H
authors.lastname: Ji
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
authors.forename: Ruey-Chyi
authors.initials: RC
authors.lastname: Su
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D060386:Sex Workers; D019562:Viral Load
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1